tbuckley/cabot-search huggingface dataset:
Endoscopic management of food impaction following endoscopic ultrasound-guided gallbladder drainage using lumen-apposing metal stent
Authors: Cecilia Binda, Chiara Coluccio, Leonardo Da Rio, Stefano Fabbri, Chiara Petraroli, Carlo Jung, Carlo Fabbri
Journal: Endoscopy (2023)

A 61-year-old man was referred to our center for severe acute cholecystitis. Given his serious comorbidities (previous dissection of an aortic aneurysm with residual disease awaiting surgical reintervention; stage 3b chronic kidney disease; alcohol-related liver disease), the patient underwent transgastric endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) using a 10 × 10 mm lumen-apposing metal stent (LAMS) ([Fig. 1]). In the following months the patient experienced two episodes of food impaction of LAMS, which were treated endoscopically with placement of two double-pigtail plastic stents coaxially through the LAMS. Then, 3 months after the procedure, the patient was admitted for a third recurrence of acute cholecystitis. Computed tomography revealed a distended gallbladder, 19 cm in the long axis and completely occupied by food ([Fig. 2]). After a multidisciplinary evaluation, surgery was again excluded, and an endoscopic attempt was performed.
Beyond rankings: Learning (more) from algorithm validation
Authors: Tobias Roß, Pierangela Bruno, Annika Reinke, Manuel Wiesenfarth, Lisa Koeppel, Peter M. Full, Bünyamin Pekdemir, Patrick Godau, Darya Trofimova, Fabian Isensee, Tim J. Adler, Thuy N. Tran, Sara Moccia, Francesco Calimeri, Beat P. Müller-Stich, Annette Kopp-Schneider, Lena Maier-Hein
Journal: Medical Image Analysis (2023)

Challenges have become the state-of-the-art approach to benchmark image analysis algorithms in a comparative manner. While the validation on identical data sets was a great step forward, results analysis is often restricted to pure ranking tables, leaving relevant questions unanswered. Specifically, little effort has been put into the systematic investigation on what characterizes images in which state-of-the-art algorithms fail. To address this gap in the literature, we (1) present a statistical framework for learning from challenges and (2) instantiate it for the specific task of instrument instance segmentation in laparoscopic videos. Our framework relies on the semantic meta data annotation of images, which serves as foundation for a General Linear Mixed Models (GLMM) analysis. Based on 51,542 meta data annotations performed on 2,728 images, we applied our approach to the results of the Robust Medical Instrument Segmentation Challenge (ROBUST-MIS) challenge 2019 and revealed underexposure, motion and occlusion of instruments as well as the presence of smoke or other objects in the background as major sources of algorithm failure. Our subsequent method development, tailored to the specific remaining issues, yielded a deep learning model with state-of-the-art overall performance and specific strengths in the processing of images in which previous methods tended to fail. Due to the objectivity and generic applicability of our approach, it could become a valuable tool for validation in the field of medical image analysis and beyond.
Hierarchically Structured Hydroxyapatite Particles Facilitate the Enhanced Integration and Selective Anti‐Tumor Effects of Amphiphilic Prodrug for Osteosarcoma Therapy
Authors: Dong Xu, Yuxin Wan, Zhenze Xie, Chang Du, Yingjun Wang
Journal: Advanced Healthcare Materials (2023)

Abstract Efficient delivery of cargo into target cells is a formidable challenge in modern medicine. Despite the great promise of biomimetic hydroxyapatite (HA) particles in tissue engineering, their potential applications in bone tumor therapy, particularly their structure–function relationships in cargo delivery to target cells, have not yet been well explored. In this study, biomimetic multifunctional composite microparticles (Bm‐cMPs) are developed by integrating an amphiphilic prodrug of curcumin with hierarchically structured HA microspheres (Hs‐hMPs). Then, the effects of the hierarchical structure of vehicles on the integration and delivery of cargo as well as the anti‐osteosarcoma (OS) effect of the composite are determined. Different hierarchical structures of the vehicles strongly influence the self‐assembly behavior of the prodrug. The flake‐like crystals of Hs‐hMPs enable the highest loading capacity and enhance the stability of the cargo. Compared to the normal cells, OS cells exhibit 3.56‐times better uptake of flake‐like Hs‐hMPs, facilitating the selective anti‐tumor effect of the prodrug. Moreover, Bm‐cMPs suppress tumor growth and metastasis by promoting apoptosis and inhibiting cell proliferation and tumor vascularization. The findings shed light on the potential application of Bm‐cMPs and suggest a feasible strategy for developing an effective targeted therapy platform using hierarchically structured minerals for OS treatment.
Liquid biopsy-based protein biomarkers for risk prediction, early diagnosis, and prognostication of cholangiocarcinoma
Authors: Ainhoa Lapitz, Mikel Azkargorta, Piotr Milkiewicz, Paula Olaizola, Ekaterina Zhuravleva, Marit M. Grimsrud, Christoph Schramm, Ander Arbelaiz, Colm J. O'Rourke, Adelaida La Casta, Malgorzata Milkiewicz, Tania Pastor, Mette Vesterhus, Raul Jimenez-Agüero, Michael T. Dill, Angela Lamarca, Juan W. Valle, Rocio I.R. Macias, Laura Izquierdo-Sanchez, Ylenia Pérez Castaño, Francisco Javier Caballero-Camino, Ioana Riaño, Marcin Krawczyk, Cesar Ibarra, Javier Bustamante, Luiz M. Nova-Camacho, Juan M. Falcon-Perez, Felix Elortza, Maria J. Perugorria, Jesper B. Andersen, Luis Bujanda, Tom H. Karlsen, Trine Folseraas, Pedro M. Rodrigues, Jesus M. Banales
Journal: Journal of Hepatology (2023)
Photothermal Propelling and Pyroelectric Potential‐Promoted Cell Internalization of Janus Nanoparticles and Pyroelectrodynamic Tumor Therapy
Authors: Junwu Wei, Yuan Liu, Yingxin Li, Zhanlin Zhang, Jie Meng, Shuang Xie, Xiaohong Li
Journal: Advanced Healthcare Materials (2023)

Cancer phototherapy experiences limitations in tissue diffusion and cell internalization of phototherapeutic agents and dose-dependent side effects. Herein, Janus pyroelectric nanoparticles (NPs) are designed to generate self-powered motion and built-in electric fields to overcome the delivery barriers. Polydopamine (PDA) layers are partially coated on tetragonal BaTiO3 (tBT) NPs to prepare Janus tBT@PDA, and Au NPs are deposited on the PDA caps to obtain Janus tBT@PDA-Au NPs. Near-infrared (NIR) illumination of tBT@PDA-Au builds in situ pyroelectric potentials on NPs, which selectively affect the membrane potential of tumor cells rather than normal cells to enhance tumor cell internalization and produce reactive oxygen species (ROS) for pyroelectric dynamic therapy (PEDT). The asymmetric photothermal effect of the Janus NPs creates thermophoretic force to propel NP motion, which enhances tumor diffusion and cellular uptake of NPs and boosts cytotoxicity and intracellular ROS levels. The inoculation of Au NPs increases the photothermal effect, exhibits larger motion velocities, produces higher pyroelectric potentials, and elevates cellular uptake rates, resulting in significant induction of tumor cell apoptosis, suppression of tumor growth, and extension of animal survival. Thus, the concise design of tBT@PDA-Au/NIR treatment has achieved thermophoretic motion-promoted tissue diffusion, built-in electric field-enhanced cell internalization, and photothermal/PEDT-synergized antitumor efficacy.
Effect of Training on Vascular Function and Repair in Heart Failure With Preserved Ejection Fraction
Authors: Andreas B. Gevaert, Birgit Böhm, Haley Hartmann, Inge Goovaerts, Tibor Stoop, Caroline M. Van De Heyning, Paul J. Beckers, Flavia Baldassarri, Stephan Mueller, Renate Oberhoffer, André Duvinage, Mark J. Haykowsky, Ulrik Wisløff, Volker Adams, Burkert Pieske, Martin Halle, Emeline M. Van Craenenbroeck
Journal: JACC Heart Failure (2023)
Vaccines for a sustainable planet
Authors: Simone Pecetta, Arindam Nandi, Charlie Weller, Vanessa Harris, Helen Fletcher, Francesco Berlanda Scorza, Mariagrazia Pizza, David Salisbury, Richard Moxon, Steve Black, David E. Bloom, Rino Rappuoli
Journal: Science Translational Medicine (2023)

The health of the planet is one objective of the United Nations’ Sustainable Development Goals. Vaccines can affect not only human health but also planet health by reducing poverty, preserving microbial diversity, reducing antimicrobial resistance, and preventing an increase in pandemics that is fueled partly by climate change.
Atrial Fibrillation Ablation for Heart Failure With Preserved Ejection Fraction
Authors: David Chieng, Hariharan Sugumar, Louise Segan, Caleb Tan, Donna Vizi, Shane Nanayakkara, Ahmed Al-Kaisey, Joshua Hawson, Sandeep Prabhu, Aleksandr Voskoboinik, Sue Finch, Joseph B. Morton, Geoffrey Lee, Justin Mariani, Andre La Gerche, Andrew J. Taylor, Erin Howden, Peter M. Kistler, Jonathan M. Kalman, David M. Kaye, Liang-Han Ling
Journal: JACC Heart Failure (2023)
Thyroid-stimulating hormone receptor signaling restores skeletal muscle stem cell regeneration in rats with muscular dystrophy
Authors: Valentina Taglietti, Kaouthar Kefi, Lea Rivera, Oriane Bergiers, Nastasia Cardone, Fanny Coulpier, Stamatia Gioftsidi, Bernadette Drayton-Libotte, Cyrielle Hou, François-Jérôme Authier, France Pietri-Rouxel, Matthieu Robert, Dominique Bremond-Gignac, Claudio Bruno, Chiara Fiorillo, Edoardo Malfatti, Peggy Lafuste, Laurent Tiret, Frédéric Relaix
Journal: Science Translational Medicine (2023)

Duchenne muscular dystrophy (DMD) is a severe and progressive myopathy leading to motor and cardiorespiratory impairment. We analyzed samples from patients with DMD and a preclinical rat model of severe DMD and determined that compromised repair capacity of muscle stem cells in DMD is associated with early and progressive muscle stem cell senescence. We also found that extraocular muscles (EOMs), which are spared by the disease in patients, contain muscle stem cells with long-lasting regenerative potential. Using single-cell transcriptomics analysis of muscles from a rat model of DMD, we identified the gene encoding thyroid-stimulating hormone receptor ( Tshr ) as highly expressed in EOM stem cells. Further, TSHR activity was involved in preventing senescence. Forskolin, which activates signaling downstream of TSHR, was found to reduce senescence of skeletal muscle stem cells, increase stem cell regenerative potential, and promote myogenesis, thereby improving muscle function in DMD rats. These findings indicate that stimulation of adenylyl cyclase leads to muscle repair in DMD, potentially providing a therapeutic approach for patients with the disease.
Soluble CTLA-4 mutants ameliorate immune-related adverse events but preserve efficacy of CTLA-4– and PD-1–targeted immunotherapy
Authors: Mingyue Liu, Xu Wang, Xuexiang Du, Wei Wu, Yan Zhang, Peng Zhang, Chunxia Ai, Martin Devenport, Juanjuan Su, Musleh M. Muthana, Lishan Su, Yang Liu, Pan Zheng
Journal: Science Translational Medicine (2023)

Immune checkpoint inhibitors (ICIs), such as nivolumab and ipilimumab, not only elicit antitumor responses in a wide range of human cancers but also cause severe immune-related adverse events (irAEs), including death. A largely unmet medical need is to treat irAEs without abrogating the immunotherapeutic effect of ICIs. Although abatacept has been used to treat irAEs, it risks neutralizing the anti–cytotoxic T lymphocyte–associated protein 4 (CTLA-4) monoclonal antibodies administered for cancer therapy, thereby reducing the efficacy of anti–CTLA-4 immunotherapy. To avoid this caveat, we compared wild-type abatacept and mutants of CTLA-4–Ig for their binding to clinically approved anti–CTLA-4 antibodies and for their effect on both irAEs and immunotherapy conferred by anti–CTLA-4 and anti–PD-1 antibodies. Here, we report that whereas abatacept neutralized the therapeutic effect of anti–CTLA-4 antibodies, the mutants that bound to B7-1 and B7-2, but not to clinical anti-CTLA-4 antibodies, including clinically used belatacept, abrogated irAEs without affecting cancer immunotherapy. Our data demonstrate that anti–CTLA-4–induced irAEs can be corrected by provision of soluble CTLA-4 variants and that the clinically available belatacept may emerge as a broadly applicable drug to abrogate irAEs while preserving the therapeutic efficacy of CTLA-4–targeting ICIs.
A cell-penetrant peptide blocking <i>C9ORF72</i> -repeat RNA nuclear export reduces the neurotoxic effects of dipeptide repeat proteins
Authors: Lydia M. Castelli, Ya-Hui Lin, Alvaro Sanchez-Martinez, Aytaç Gül, Kamallia Mohd Imran, Adrian Higginbottom, Santosh Kumar Upadhyay, Nóra M. Márkus, Raquel Rua Martins, Johnathan Cooper-Knock, Claire Montmasson, Rebecca Cohen, Amy Walton, Claudia S. Bauer, Kurt J. De Vos, Richard J. Mead, Mimoun Azzouz, Cyril Dominguez, Laura Ferraiuolo, Pamela J. Shaw, Alexander J. Whitworth, Guillaume M. Hautbergue
Journal: Science Translational Medicine (2023)

Hexanucleotide repeat expansions in C9ORF72 are the most common genetic cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Studies have shown that the hexanucleotide expansions cause the noncanonical translation of C9ORF72 transcripts into neurotoxic dipeptide repeat proteins (DPRs) that contribute to neurodegeneration. We show that a cell-penetrant peptide blocked the nuclear export of C9ORF72 -repeat transcripts in HEK293T cells by competing with the interaction between SR-rich splicing factor 1 (SRSF1) and nuclear export factor 1 (NXF1). The cell-penetrant peptide also blocked the translation of toxic DPRs in neurons differentiated from induced neural progenitor cells (iNPCs), which were derived from individuals carrying C9ORF72 -linked ALS mutations. This peptide also increased survival of iNPC-differentiated C9ORF72-ALS motor neurons cocultured with astrocytes. Oral administration of the cell-penetrant peptide reduced DPR translation and rescued locomotor deficits in a Drosophila model of mutant C9ORF72-mediated ALS/FTD. Intrathecal injection of this peptide into the brains of ALS/FTD mice carrying a C9ORF72 mutation resulted in reduced expression of DPRs in mouse brains. These findings demonstrate that disrupting the production of DPRs in cellular and animal models of ALS/FTD might be a strategy to ameliorate neurodegeneration in these diseases.
Vitamin B5 and succinyl-CoA improve ineffective erythropoiesis in <i>SF3B1</i> -mutated myelodysplasia
Authors: Syed A. Mian, Céline Philippe, Eleni Maniati, Pantelitsa Protopapa, Tiffany Bergot, Marion Piganeau, Travis Nemkov, Doriana Di Bella, Valle Morales, Andrew J. Finch, Angelo D’Alessandro, Katiuscia Bianchi, Jun Wang, Paolo Gallipoli, Shahram Kordasti, Anne Sophie Kubasch, Michael Cross, Uwe Platzbecker, Daniel H. Wiseman, Dominique Bonnet, Delphine G. Bernard, John G. Gribben, Kevin Rouault-Pierre
Journal: Science Translational Medicine (2023)

Patients with myelodysplastic syndrome and ring sideroblasts (MDS-RS) present with symptomatic anemia due to ineffective erythropoiesis that impedes their quality of life and increases morbidity. More than 80% of patients with MDS-RS harbor splicing factor 3B subunit 1 (SF3B1) mutations, the founder aberration driving MDS-RS disease. Here, we report how mis-splicing of coenzyme A synthase ( COASY ), induced by mutations in SF3B1 , affects heme biosynthesis and erythropoiesis. Our data revealed that COASY was up-regulated during normal erythroid differentiation, and its silencing prevented the formation of erythroid colonies, impeded erythroid differentiation, and precluded heme accumulation. In patients with MDS-RS, loss of protein due to COASY mis-splicing led to depletion of both CoA and succinyl-CoA. Supplementation with COASY substrate (vitamin B5) rescued CoA and succinyl-CoA concentrations in SF3B1 mut cells and mended erythropoiesis differentiation defects in MDS-RS primary patient cells. Our findings reveal a key role of the COASY pathway in erythroid maturation and identify upstream and downstream metabolites of COASY as a potential treatment for anemia in patients with MDS-RS.
Short-Term Lactate Kinetics in Patients With Cardiogenic Shock
Authors: Jonas Sundermeyer, Salim Dabboura, Jessica Weimann, Benedikt N. Beer, Peter Moritz Becher, Moritz Seiffert, Paulus Kirchhof, Stefan Blankenberg, Dirk Westermann, Benedikt Schrage
Journal: JACC Heart Failure (2023)
Distinct Mechanisms Responsible for the Increase in Glucose Production and Ketone Formation Caused by Empagliflozin in T2DM Patients
Authors: Siham Abdelgani, Ahmed Khattab, John Adams, Mohamed Abu-Farha, Giuseppe Daniele, Fahd Al-Mulla, Stefano Del Prato, Ralph A. DeFronzo, Muhammad Abdul-Ghani
Journal: Diabetes Care (2023)

OBJECTIVE To examine the mechanisms responsible for the increase in glucose and ketone production caused by empagliflozin in patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS Twelve subjects with T2DM participated in two studies performed in random order. In study 1, endogenous glucose production (EGP) was measured with 8-h infusion of 6,6,D2-glucose. Three hours after the start of 6,6,D2-glucose infusion, subjects ingested 25 mg empagliflozin (n = 8) or placebo (n = 4), and norepinephrine (NE) turnover was measured before and after empagliflozin ingestion with 3H-NE infusion. Study 2 was similar to study 1 but performed under pancreatic clamp conditions. RESULTS When empagliflozin was ingested under fasting conditions, EGP increased by 31% in association with a decrease in plasma glucose (−34 mg/dL) and insulin (−52%) concentrations and increases in plasma glucagon (+19%), free fatty acid (FFA) (+29%), and β-hydroxybutyrate (+48%) concentrations. When empagliflozin was ingested under pancreatic clamp conditions, plasma insulin and glucagon concentrations remained unchanged, and the increase in plasma FFA and ketone concentrations was completely blocked, while the increase in EGP persisted. Total-body NE turnover rate was greater in subjects receiving empagliflozin (+67%) compared with placebo under both fasting and pancreatic clamp conditions. No difference in plasma NE concentration was observed in either study. CONCLUSIONS The decrease in plasma insulin and increase in plasma glucagon concentration caused by empagliflozin is responsible for the increase in plasma FFA concentration and ketone production. The increase in EGP caused by empagliflozin is independent of the change in plasma insulin or glucagon concentrations and is likely explained by the increase in NE turnover.
Tirzepatide Reduces Appetite, Energy Intake, and Fat Mass in People With Type 2 Diabetes
Authors: Tim Heise, J. Hans DeVries, Shweta Urva, Jing Li, Edward J. Pratt, Melissa K. Thomas, Kieren J. Mather, Chrisanthi A. Karanikas, Julia Dunn, Axel Haupt, Zvonko Milicevic, Tamer Coskun
Journal: Diabetes Care (2023)

OBJECTIVE To evaluate the effects of tirzepatide on body composition, appetite, and energy intake to address the potential mechanisms involved in body weight loss with tirzepatide. RESEARCH DESIGN AND METHODS In a secondary analysis of a randomized, double-blind, parallel-arm study, the effects of tirzepatide 15 mg (N = 45), semaglutide 1 mg (N = 44), and placebo (N = 28) on body weight and composition, appetite, and energy intake were assessed at baseline and week 28. RESULTS Tirzepatide treatment demonstrated significant reductions in body weight compared with placebo and semaglutide, resulting in greater fat mass reduction. Tirzepatide and semaglutide significantly reduced appetite versus placebo. Appetite scores and energy intake reductions did not differ between tirzepatide and semaglutide. CONCLUSIONS Differences in energy intake during ad libitum lunch were not sufficient to explain the different weight outcomes. Further evaluation is needed to assess mechanistic differences related to tirzepatide actions on 24-h energy intake, substrate utilization, and energy expenditure.
When You SPRINT, It's Good to Know the Goal as Well as the Goal Line
Authors: Josephine P. Briggs, Peter B. Imrey
Journal: Journal of the American Society of Nephrology (2023)

1Journal of the American Society of Nephrology, Bernard, Maine 2Department of Quantitative Health Sciences, Lerner Research Institute and Mellen Center for Multiple Sclerosis Treatment and Research, Neurological Institute, Cleveland Clinic, Cleveland, Ohio 3Department of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio Correspondence: Dr. Josephine Briggs, PO Box 125 Bernard, ME 04612. Email: [email protected] See related article, “Intensive BP Control in Patients with CKD and Risk for Adverse Outcomes,” on pages 385–393.
A Single-cell Atlas Identifies Pretreatment Features of Primary Imatinib Resistance in Chronic Myeloid Leukemia
Authors: Vaidehi Krishnan, Florian Schmidt, Zahid Nawaz, Prasanna Nori Venkatesh, Kian Leong Lee, Xi Ren, Zhu En Chan, Mengge Yu, Meera Makheja, Nirmala Arul Rayan, Michelle Gek Liang Lim, Alice Man Sze Cheung, Sudipto Bari, Wee Joo Chng, Hein Than, John Ouyang, Owen Rackham, Tuan Zea Tan, William Ying Khee Hwang, Charles Chuah, Shyam Prabhakar, S. Tiong Ong
Journal: Blood (2023)
PKM2 allosteric converter: A self-assembly peptide for suppressing renal cell carcinoma and sensitizing chemotherapy
Authors: Lu Wang, Bo Fu, Da-Yong Hou, Yu-Lin Lv, Guang Yang, Cong Li, Jia-Chen Shen, Bin Kong, Li-Bo Zheng, Yu Qiu, Hong-Lei Wang, Chen Liu, Jian-Ji Zhang, Shi-Yu Bai, Li-Li Li, Hao Wang, Wan-Hai Xu
Journal: Biomaterials (2023)
Response to: Elevated L1 expression in ataxia telangiectasia likely explained by an RNA-seq batch effect
Authors: Takehiro Takahashi, Milan Stoiljkovic, Eric Song, Xiao-Bing Gao, Yuki Yasumoto, Eriko Kudo, Fernando Carvalho, Yong Kong, Annsea Park, Marya Shanabrough, Klara Szigeti-Buck, Zhong-Wu Liu, Ashley Kristant, Yalan Zhang, Parker Sulkowski, Peter M. Glazer, Leonard K. Kaczmarek, Tamas L. Horvath, Akiko Iwasaki
Journal: Neuron (2023)
A spinal muscular atrophy modifier implicates the SMN protein in SNARE complex assembly at neuromuscular synapses
Authors: Jeong-Ki Kim, Narendra N. Jha, Tomoyuki Awano, Charlotte Caine, Kishore Gollapalli, Emily Welby, Seung-Soo Kim, Andrea Fuentes-Moliz, Xueyong Wang, Zhihua Feng, Fusako Sera, Taishi Takeda, Shunichi Homma, Chien-Ping Ko, Lucia Tabares, Allison D. Ebert, Mark M. Rich, Umrao R. Monani
Journal: Neuron (2023)
Data-driven subgroups of prediabetes and the associations with outcomes in Chinese adults
Authors: Ruizhi Zheng, Yu Xu, Mian Li, Zhengnan Gao, Guixia Wang, Xinguo Hou, Li Chen, Yanan Huo, Guijun Qin, Li Yan, Qin Wan, Tianshu Zeng, Lulu Chen, Lixin Shi, Ruying Hu, Xulei Tang, Qing Su, Xuefeng Yu, Yingfen Qin, Gang Chen, Xuejiang Gu, Feixia Shen, Zuojie Luo, Yuhong Chen, Yinfei Zhang, Chao Liu, Youmin Wang, Shengli Wu, Tao Yang, Qiang Li, Yiming Mu, Jiajun Zhao, Chunyan Hu, Xiaojing Jia, Min Xu, Tiange Wang, Zhiyun Zhao, Shuangyuan Wang, Hong Lin, Guang Ning, Weiqing Wang, Jieli Lu, Yufang Bi
Journal: Cell Reports Medicine (2023)

Prediabetes and its pathophysiology remain important issues. We aimed to examine the cluster characteristics of prediabetes and explore their associations with developing diabetes and its complications based on 12 variables representing body fat, glycemic measures, pancreatic β cell function, insulin resistance, blood lipids, and liver enzymes. A total of 55,777 individuals with prediabetes from the China Cardiometabolic Disease and Cancer Cohort (4C) were classified at baseline into six clusters. During a median of 3.1 years of follow-up, significant differences in the risks of diabetes and its complications between clusters were observed. The odds ratios of diabetes stepwisely increase from cluster 1 to cluster 6. Clusters 1, 4, and 6 have increased chronic kidney diseases risks, while the prediabetes in cluster 4, characterized by obesity and insulin resistance, confers higher risks of cardiovascular diseases compared with others. This subcategorization has potential value in developing more precise strategies for targeted prediabetes prevention and treatment.